Palladium-Catalyzed Enantioselective α-Arylation of α-Fluoroketones

Palladium-Catalyzed Enantioselective α-Arylation of α-Fluoroketones

J. Am. Chem. Soc. 2016138, 15980–15986.

The transition metal-catalyzed α-arylation of carbonyl compounds is a widely practiced method for C–C bond formation. Several enantioselective versions of this process have been reported, but intermolecular, enantioselective coupling reactions of aryl electrophiles with α-fluoro carbonyl compounds have yet to be disclosed. We report enantioselective coupling of aryl and heteroaryl bromides and triflates with α-fluoro indanones catalyzed by palladium complexes of a structurally novel BINOL-derived hindered monophosphine and Segphos, respectively. The enolates were generated directly from α-fluoro indanones in the presence of potassium phosphate base during the reactions. We also report that reactions of α-fluoro tetralones occur in high yields and enantioselectivities when conducted with enolates generated by elimination of trifluoroacetate from a trifluoromethyl β-diketone hydrate. These reactions were catalyzed by palladium complexes of the commercially available bisphosphine Difluorphos. Thus, the formation of enantioenriched α-aryl-α-fluoro ketones can be readily achieved by C–C bond formation when the appropriate palladium catalyst and α-fluoro enolate precursor were used.

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